STRUCTURE-ACTIVITY RELATIONS IN VITAMIN E SERIES .2. DERIVATIVES OF ALPHA TOCOPHEROL SUBSTITUTED AT 5-METHYL GROUP

Several derivatives of α-tocopherol substituted at the 5-melhyl group were synthesized from the common intermediate, 5-chloromethyl-7,8-dimethyltocol acetate. These derivatives were evaluated for their activities in protecting rabbits against vitamin E deficiency induced muscular dystrophy and rats against dietary necrotic liver degeneration. It was found that the phytyl side chain of (dl-α-tocopherol contributes to its biological activity in these animal systems, and that the presence of an intact 5-methyl group, although not essential for activity, greatly enhances it. Several of these derivatives were active in both test systems, while others were inactive. Some crossover of activities was seen in muscular dystrophy in the rabbit and dietary liver necrosis in the rat. © 1969, American Chemical Society. All rights reserved.